PROJECT 3 PROJECT SUMMARY Impact of Environmental Modifications on Pathogenesis and Immunity of Plasmodium falciparum and P. vivax Malaria Hydropower dam and irrigation initiatives to improve and sustain agricultural productivity are underway in Ethiopia and Kenya. However, there is very limited knowledge of how these water and land use modifications will affect diverse malaria ecosystems and impact ongoing vector interventions that have decreased but not eliminated malaria transmission. Research in this project will address topics pertinent to understanding how rapid changes in intensity and geospatial features of Plasmodium falciparum vivax and P. vivax transmission resulting from environmental modifications impact naturally acquired immunity (NAI) to malaria disease pathogenesis and parasite transmission from humans to mosquitoes. From a translational perspective, the goals are to 1) develop, evaluate and validate in vitro correlates of NAI adaptable to standardized formats as population surveillance and diagnostic tools that could be used to predict resurgences or reductions of malaria morbidity, and 2) advance understanding of naturally acquired P. falciparum antibody-mediated transmission reducing activity. From a basic perspective, our goals are to 1) define the mechanistic roles of antibodies and complement in malaria immunity, and 2) fill in major gaps of knowledge related to NAI to P. vivax pathogenesis in Africa. These goals will be achieved through a collaboration involving field and laboratory facilities in two malaria endemic sites in western Kenya and three malaria endemic sites in Ethiopia with malaria research teams in the U.S. and Australia that have long standing working relationships with research scientists and malaria public health experts in Ethiopia and Kenya. This is integrated with the Epidemiology project, which will generate biological samples, clinical data, and antibody seroconversion data, and the Transmission project, which will determine whether vector species composition, biting behavior and spatial patterns of exposure to anopheline mosquitoes correlate with changes in transmission reducing immunity. The Administrative and Data Management and Biostatistics Cores will be critical to the logistics, management, and scientific value of this project.